Hydroxychloroquine and Azithromycin as a treatment of COVID-19: Updated on 3/29/20

First of all, credit to the authors. Huge hat tip to them.

Gautret et al. (2020) Hydroxychloroquine and azithromycin as a treatment of COVID‐19: results of an open‐label non‐randomized clinical trial. International Journal of Antimicrobial Agents – In Press 17 March 2020 – DOI : 10.1016/j.ijantimicag.2020.105949

First of all, there are a substantial amount of limitations to the study but in my opinion, not medical advice, it provides a glimmer of hope. 

Let's begin

Where was it performed: French study (thank youuuuuu!)

Population: NOT ICU Patients! But we've learned that non-ICU patients become ICU patients extremely quick! 

n=36 (20 hydroxychloroquine, 16 control)

How did the determine the Viral load? Nasopharyngeal swabs daily
Questions I have: 6 patients (originally n=42) lost to follow up. Patients who were transferred to the ICU were considered to be "lost to follow-up" (n=3). I can't tell if the one patient who died was transferred to the ICU. Hopefully the edits will sort this out. Why didn't they just follow those patients who ended up in the ICU?
Age groups were not matched but this would favor the control group as the experimental group was older. More were male in the experimental group which we assume that males get this worse than females. More asymptomatic patients in the control group, also bodes worse for the experimental arm.

3 classifications: asymptomatic, upper respiratory, lower respiratory

Regimen:

Hydroxychloroquine 600mg daily (200mg TID x 10 days)

+/- azithromycin depending on clinical presentation (500mg on day 1, 250mg x 4 days) 

Results: 

At day 6, 70% of hydroxychloroquine group were virologically cured vs. 12.5% in control group (p=0.001) NNT = 1.7!! 

100% of hydroxychloroquine + azithromycin were virologically cured vs 57.1% in the hydroxychloroquine only group vs. 12.5% in the control group (p0.001)

Drug effect was higher in URI and LRI than asymptomatic patients (p=0.05)

Starts working in 3-6 days per this data. 

Careful with the QT prolongation on the EKG! Replete the Mg as needed for this. Monitor liver function. My pharmacy friends can contribute some more adverse effect stuff like retinopathy, etc.  

I cannot make any recommendations as I do not give medical advice but I know what I would do with this data to save a life. 

-EJ

LINK TO FULL FREE PDF!!

An Update on 3/29/2020

We have an update now from the same researchers in France. It's a free PDF and I recommend you read it yourself. Don't trust me.

Interesting that the authors mention potentially using ARBs, metformin, and statins as many have directly messaged me asking what I thought on these particular families of treatments. This study has me scratching my head. Their first study seemed like they rushed it out the door to start some more broad research. This study seems like they're deliberately hiding things from us or trying to remain obscure.

Methods:This is an observational study, meaning they didn't have any controls.

80% of patients appear to have gotten a CT of the chest and (almost) every patient had a daily nasopharyngeal swab.

They all got an EKG before treatment and two days after treatment began. They had criteria to not start therapy based on some findings listed in the article.

Treatment regimen:Hydroxychloroquine 200mg three time a day for 10 days
Azithromycin 500mg on day 1, then 250 daily for 4 days


End points (these are not your typical endpoints):

Clinical Outcome (oxygen therapy or ICU transfer)
Contagiousness by PCR and culture
Length of stay in the ID ward

Things to know:n=80

4 patients were asymptomatic carriers (then why were they in the COVID unit?)

92% of the patients were less ill based on their made up NEWS score

52.8% had lower respiratory infections/pneumonia.

Results:
We don't have any controls to know if this is the normal course of the infection or if the hydroxychloroquine actually worked or not. I forgive them for not having controls in the prior study but this is now too much.

93.8% were discharged from a low NEWS score. Don't forget that 92% had a low news score to begin with!

3 patients still ended up in the ICU.

The nasopharyngeal viral load fell. Sure. Cool. Thanks. But does this normally fall at this rate without treatment? We need controls. Is the decrease in contagiousness the normal evolution or the drugs working? We don't know. No controls.

I'm tired of reviewing this study. You all get my point. I am in favor of trying it, but I feel like there's some academic dishonesty happening here.

I really want this to work. I really really do. We need some good news but we also need to solidify our management with better data.


Link to full FREE PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

SCCM/ESICM Guidelines on COVID-19

The Society of Critical Care Medicine and the European Society of Intensive Care Medicine came together for these guidelines regarding COVID-19. Thank goodness they didn’t include 30cc/kg bolus for an elevated lactate 🤣. I figure this will be revised as more data comes out in the upcoming weeks, especially regarding the therapies as Kaletra was recently mostly disproven to have a benefit. 

Many of the recommendations included are not new to us who are on the cutting edge of Critical Care medicine but it’s always good to share concepts such as conservative fluid management , using balanced crystalloids over 0.9% saline, not using dopamine. They have relaxed their MAP goals. I wonder if that has to do with the new trials on MAP goals in the elderly since this predominantly affects the elderly. Hmmmm need to look into that some more. They also stress the importance of proning patients. If your shop doesn’t prone, I have posts and guidelines for this on this page and my website. 

I’ll try hard to answer your questions but there’s a lot going on and I’m quite busy with a number of other tasks I’m helping out with. Best of luck to you all!

- EJ

Link to FULL FREE PDF

Link to SCCM Page

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

Kaletra (lopinavir–ritonavir) did not work in COVID-19 :(

Trials are starting to come in. I'm not going to belabor the fact but it appears that Kaletra, also known as lopinavir–ritonavir (400 mg and 100 mg, respectively) does not work for patients with COVID-19. I'm not going to dissect the article for you all as this is more intended to be a news bulletin of sorts. It is important to note that they used the sickest of the sick patients in the study. This does not mean that data in the future will say that it cannot help in those less ill but I really don’t see anyone trying at this point.

No difference in clinical improvement, mortality, nor decrease in viral load. Please read the article for yourself if you're using this at your institution. I do not provide medical advice. A 🎩 tip to the authors.

I have seen it in the protocols for several institutions that have been sent to me. I will never EVER disclose any information that you all send me via email without discussing it with you all first.

Tomorrow is my 38th birthday so I'll be celebrating it with a ton of social distancing and maybe a trip to a more secluded beach.

Thank you for your support. The page is growing fast but I wish it was slower and I didn’t have so much to post about regarding a deadly virus that is changing our lives so rapidly. ☹️

-EJ

Link to Abstract

Link to FULL FREE PDF

Cao B, Wang Y, Wen D, et al. A trial of lopinavir–ritonavir in adults hospitalized with severe Covid-19. N Engl J Med. DOI: 10.1056/NEJMoa2001282.

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

COVID-19: Airborne or Droplet Precautions

This is a widely contested topic that I feel we still do not know the full answer on, but I am feeling better about.

As of right now, though, it seems hospital administrators have a leg to stand on when they recommend face masks for the majority of cases and N95's/respirators for NIV, intubations, bronchs, nebs, etc. I don't know if this is an official recommendation by any agency, but patients who have COVID-19 or are being ruled out for this should wear a mask in the hospital and outside the hospital. 

The flip flopping of policies occurs as we learn more data. It seems shady to me that they flipped their policies as shortages occurred, but it seems as if it's defensible at this time.

WHO: The February 27, 2020 guidance paper states:

"Healthcare workers involved in the direct care of patients should use the following PPE: gowns, gloves, medical mask and eye protection (goggles or face shield)."

"Specifically, for aerosol-generating procedures (e.g., tracheal intubation, non-invasive ventilation, tracheostomy, cardiopulmonary resuscitation, manual ventilation before intubation, bronchoscopy) healthcare workers should use respirators, eye protection, gloves and gowns; aprons should also be used if gowns are not fluid resistant."

CDC: updated recommendations on March 10, 2020:

"Based on local and regional situational analysis of PPE supplies, facemasks are an acceptable alternative when the supply chain of respirators cannot meet the demand.
During this time, available respirators should be prioritized for procedures that are likely to generate respiratory aerosols, which would pose the highest exposure risk to HCP."

Essentially, they are acknowledging that we are being put at risk due to the lack of masks.

The most recent stir and adding to the controversy was a recent publication NEJM published on 3/17/20 which states:

"SARS-CoV-2 remained viable in aerosols throughout the duration of our experiment (3 hours)"

"The half-lives of SARS-CoV-2 and SARS-CoV-1 were similar in aerosols, with median estimates of approximately 1.1 to 1.2 hours"

"Our results indicate that aerosol and fomite transmission of SARS-CoV-2 is plausible, since the virus can remain viable and infectious in aerosols for hours and on surfaces up to days (depending on the inoculum shed)"

The key point is that the authors went out of their way to both nebulize the virus AND fed it into a Goldberg drum to further disperse it (I don't know what that is and google wasn't too helpful).

It is admittedly outside my scope of knowledge how to interpret the titers in the air, but it seems as if it's there and transmissible to us, the boots on the ground. I cannot make a concrete declaration based on my level of knowledge. I'd welcome your interpretation. I am curious to see how the ever-intelligent people in the CDC and WHO react to this data and possibly adapt their recommendations. 

We should also reach out to the local news agencies to assist us in asking the N95 hoarders to donate their extras to the local hospitals. We need to protect each other. 

-EJ

Link to the WHO Interim Guidance Paper

Link to the CDC Information

Link to the NEJM Abstract

Link to the NEJM PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

How to take off your PPE after caring for COVID-19 patients

The first time I walked into a the room of a patient with suspected COVID-19 I was very methodical with every step. I had done my required reading. I had an N95, a face shield over that, a hair net, the stupid yellow contact gown, double gloves. At the same time I felt naked. I had seen the people on TV and in other countries in basically hazmat suits. The uncertainty was driving me bonkers but I needed to take care of the patient ASAP. The nurse and I got everything together and we went in. We took care of the patient. When it was time to come out, the same methodical steps took place. But somewhat in reverse. It’s hot in there with all that gear when you have to put on the sterile gown for procedures and the sterile gloves on top of my double gloves. Since the I have walked into a number of rooms and am getting the feeling that this is going to be the new normal for the next few months. I felt it was important to do a second post today to share the CDC guidelines on how to put on and take off the personal protective equipment. I have attached the images from this as well. Feel free to share with your friends.

I was inspired to create this post after seeing @doctorwarsgame’s similar post. I must give him credit. I also sent meme, as I am not someone who creates them on this medium, to @bedsideroundz for his approval. He actually was the one who suggested that I use it to teach people the correct way to do it.

Thank you all for your support.

CDC Guidelines for Healthcare Personnel PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

COVID-19: Don't order unnecessary nebulizations!!

Colleagues, I know that lots of us have knee-jerk tendencies to order nebulizations on everyone who is on a ventilator, NIV, or any type of shortness of breath under the sun because it makes us feel warm and fuzzy inside where we say "I did something". This behavior needs to stop. We are potentially aerosolizing the virus and putting our teammates at risk. COVID-19 does not appear to be an airborne virus, it is a droplet precaution virus. We need to take care of our patients but we can't go down ourselves. Let stop with the unnecessary tests and treatments. We should not have our respiratory therapists and nurses being unnecessarily exposed, simply the process of going in and out of the room, for no beneficial reason to the patient. We're at war here. We need all of our soldiers intact to help us in this fight. Stop the unnecessary practices.

This data is pulled from the SARS outbreak. Both of these articles are free.

- EJ



Link to FULL FREE Article


Seto WH, Tsang D, Yung RW, et al. Effectiveness of precautions against droplets and contact in prevention of nosocomial transmission of severe acute respiratory syndrome (SARS). Lancet. 2003;361(9368):1519–1520. doi:10.1016/s0140-6736(03)13168-6



Link to FULL FREE Article

Loeb M, McGeer A, Henry B, et al. SARS among critical care nurses, Toronto. Emerg Infect Dis. 2004;10(2):251–255. doi:10.3201/eid1002.030838

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.

US Ventilator Resources for COVID-19

I have purposefully kept quite and obtained data regarding the COVID-19 outbreak. I don't like to open my mouth or write unless I have a pretty good grasp on what is going on. My crew and I are going to be on the front lines when this thing hits, and I believe it's going to hit. I hope I'm wrong. The majority of the people who follow my page are going to be on the front lines, too. That being said, the system is going to be stressed for resources. I have already heard from different regions of the country and I'm concerned. 

The Society of Critical Care Medicine just sent out an email discussing resource availability. 
I'm more concerned after reading this letter. The data is extremely outdated in many parts. The numbers are obtained from the American Hospital Association which were obtained via voluntary survey. Here's an example: in 2009 we had, in the country, 62000 vents. We have almost 99000 old vents (I don't know what this means nor where they are bc they mention that 23k are NIV, 33k are automatic resuscitators, and 8500 are CPAP units). The strategic national stockpile has 8900 ventilators ready for deployment. 

We're looking at an estimated total of 200,000 ventilators in the country. 

They crunched the numbers based on the number of people who end up on the vent with COVID-19. We could reasonably expect 960,000 to require ventilatory support. I don't know if ventilatory support means non-invasive ventilation + high flow nasal cannula + mechanical ventilation or just MV. I've read about avoiding NIV and HFNC as they aerosolize the virus but I need to learn more. 

It's great to see that we have more critical care beds per capita than anywhere else in the world, but who is going to take care of those patients when there's a limited supply of healthcare professionals who are trained to take care of the critically ill? 

I see this as us being in deep trouble and that all the lockdowns, travel bans, cancellations of everything being justified. My respect for this is growing as I become more educated. I was supposed to go to Greece on Monday. I was bummed out but I reminded myself that this is not about me. 

Stay safe, everyone. 

-EJ

Link to PDF

Although great care has been taken to ensure that the information in this post is accurate, eddyjoemd, LLC shall not be held responsible or in any way liable for the continued accuracy of the information, or for any errors, omissions or inaccuracies, or for any consequences arising therefrom.